Acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus type 1 (HIV-1) infection is arguably the greatest epidemic currently facing the human race. Globally, AIDS causes more deaths than any other infectious disease, and the number of new cases continues to rise at alarming rates every year.

In the United States, AIDS is the second leading cause of death in persons 25-44 years of age (car accidents and other accidents being first). In many parts of Africa, AIDS is the leading cause of death.

Today, over 42 million people have been infected with HIV. One of the most tragic facts about AIDS, compared to other leading causes of death such as cancer and heart disease, is that most infections and deaths occur in persons less than 25 years of age. Approximately 3 million children under the age of 15 are infected with HIV-1.

More than a fourth of all infected persons are unaware that they are infected. This means that they can unknowingly spread the disease.

Infectious Agent

AIDS is caused by HIV-1. HIV is a retrovirus that incorporates its genetic material into that of host cells, making it very difficult for the immune system to eliminate the virus from the body. To date, there are no known cases where a patient has successfully cleared the infection.

HIV-1 evolved from a closely related virus from chimpanzees known as simian immunodeficiency virus (SIV). Several types of SIV exist in many different species of African nonhuman primates (both apes and monkeys). In some nonhuman primates, SIV causes AIDS identical to that of HIV-1 infection in humans. In others, the virus persists for years in the host without causing severe immunodeficiency. Nonhuman primates are thus widely used to study how and why the virus causes disease in some species and not in others.

Transmission

The vast majority of HIV-1 infections occur as a result of vaginal (heterosexual) sexual transmission. Approximately half of the HIV cases in the world today are in women.

HIV-1 is most often transmitted by sexual contact (vaginal, anal or oral sex). However, the virus can also be transmitted by direct contact with infected blood when re-using contaminated needles or when receiving transfusions of contaminated blood.

Infants born to infected mothers are infected either during birth or through ingestion of HIV-1 infected milk soon after birth.

HIV is not known to be transmitted by mosquitoes or other insects. HIV is also not spread through the air, so casual contact (handshakes, coughing, sneezing, kissing, etc.) does not transmit the infection.

The Disease

HIV can enter the body through mucosal tissues (vagina, rectum or oral tissues) or the blood. Once it enters the body, it rapidly spreads to the intestines and other lymphoid tissues where it immediately infects and destroys the body's CD4+ T cells (T helper cells). These T helper cells are essential in fighting all infections. Counting the number of CD4+ T cells in the blood is one method by which clinicians monitor the status of HIV-1 infection. The body responds to the loss of CD4+ T cells by trying to replenish them. In the early stages of infection, the production of new cells almost equals the rate of loss, so there is a long period of time during which the infected person does not feel sick or show any signs of the infection.

However, after several months or years, the CD4+ T cell pool eventually becomes exhausted and the immune system collapses. Bacteria, fungi and other organisms in the environment begin to establish infections in the now immune-compromised person. These infections are called "opportunistic infections" because, in most cases, these organisms only cause infections when there is an opportunity to do so (such as in an immune-compromised patient).

The signs and symptoms of HIV-1 infection and even the cause of death are usually related to opportunistic infections which include pneumonia, intestinal disease (diarrhea and wasting), and/or damage to the central nervous system.

Treatment

Currently, there is neither a cure nor a vaccine for HIV. Although scientists have developed a number of anti-viral therapies that partially control the infection and extend the life of infected patients, these drugs are expensive and have a number of serious side effects.

One major obstacle to developing a cure is that the virus incorporates its genes into the DNA of cells of infected persons. It can lie dormant in the body (latently infected cells) and serve as a continual source of viral replication and infection of other cells. These cells cannot be distinguished from other cells of the body, so eliminating the virus from patients is currently not possible.

Developing a vaccine is similarly elusive, partially because HIV targets and destroys the very cells responsible for generating immune responses. Furthermore, the virus mutates rapidly, so the immune system is not able to keep up with the changes the virus makes to evade immune responses. For example, persons require a different vaccine for influenza each year because of the rate at which this virus mutates, and HIV mutates faster than influenza. When compared to other viruses, HIV has a number of differences that make it particularly elusive. Developing an effective vaccine for HIV is likely to require major advances in immunology research.

Our Research

We use nonhuman primates to study HIV pathogenesis (how the virus causes disease). Understanding how the virus causes disease forms the foundation for the development of treatments and vaccines for HIV.

The use of nonhuman primates for AIDS research is vital for testing vaccines, treatments and preventatives. Other laboratory animals (e.g., rodents) cannot be infected with HIV (or the closely related SIV), and cell cultures simply do not provide critical information on prevention, vaccines or even treatment. For example, drugs that inhibit infection or prevent viral replication in tissue cultures have often proven to have disastrous effects when used in human patients.

The use of nonhuman primates also provides important information that simply cannot be discovered by studying HIV-infected humans. For example, using the monkey model, we discovered that the intestinal tract was the major target organ for HIV replication and persistence. Several years later (2004), HIV researchers confirmed this in HIV-infected humans. Based upon our findings in monkeys, vaccine research and therapeutic strategies are now largely being redirected to monitor intestinal immune responses.

We are currently testing a number of new therapies and vaccines. We are testing new preventatives for HIV infection, which may eventually slow the spread of the epidemic. Using nonhuman primates, we have also demonstrated that molecular fusion inhibitors may be useful as microbicides to prevent HIV transmission and infection. Application of these microbicides to the vagina of macaques resulted in protection from vaginal transmission to monkeys. The hopes are that similar compounds may soon be available to protect women from HIV transmission.